rs6465657

Variant names:

• chr7-98187015-C-T
• rs6465657
• NM_014916.4:c.998+17C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014916.4(LMTK2):​c.998+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,596,282 control chromosomes in the GnomAD database, including 196,711 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (13406 hom., cov: 33)
  • Exomes 𝑓: 0.49 (183305 hom.)
• Consequence: LMTK2 NM_014916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 171 publications found

Genes affected

LMTK2 (HGNC:17880): (lemur tyrosine kinase 2) The protein encoded by this gene belongs to the protein kinase superfamily and the protein tyrosine kinase family. It contains N-terminal transmembrane helices and a long C-terminal cytoplasmic tail with serine/threonine/tyrosine kinase activity. This protein interacts with several other proteins, such as Inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI. It phosporylates other proteins, and is itself also phosporylated when interacting with cyclin-dependent kinase 5 (cdk5)/p35 complex. This protein involves in nerve growth factor (NGF)-TrkA signalling, and also plays a critical role in endosomal membrane trafficking. Mouse studies suggested an essential role of this protein in spermatogenesis. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMTK2	NM_014916.4	c.998+17C>T		intron_variant	Intron 9 of 13	ENST00000297293.6	NP_055731.2
LMTK2	XM_011515981.4	c.992+17C>T		intron_variant	Intron 9 of 13		XP_011514283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMTK2	ENST00000297293.6	c.998+17C>T		intron_variant	Intron 9 of 13	1	NM_014916.4	ENSP00000297293.5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56662 AN: 152012 Hom.: 13407 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.430

GnomAD2 exomes AF: 0.405 AC: 96530 AN: 238114 AF XY: 0.415

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.472

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.479

GnomAD4 exome AF: 0.487 AC: 703442 AN: 1444152 Hom.: 183305 Cov.: 29 AF XY: 0.483 AC XY: 346528 AN XY: 717764

African (AFR) AF: 0.0969 AC: 3173 AN: 32742

American (AMR) AF: 0.260 AC: 10721 AN: 41198

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 15020 AN: 25572

East Asian (EAS) AF: 0.120 AC: 4735 AN: 39390

South Asian (SAS) AF: 0.237 AC: 19629 AN: 82698

European-Finnish (FIN) AF: 0.479 AC: 25448 AN: 53154

Middle Eastern (MID) AF: 0.613 AC: 3489 AN: 5694

European-Non Finnish (NFE) AF: 0.537 AC: 593007 AN: 1104024

Other (OTH) AF: 0.473 AC: 28220 AN: 59680

GnomAD4 genome AF: 0.372 AC: 56645 AN: 152130 Hom.: 13406 Cov.: 33 AF XY: 0.363 AC XY: 27013 AN XY: 74360

African (AFR) AF: 0.110 AC: 4584 AN: 41504

American (AMR) AF: 0.351 AC: 5369 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2015 AN: 3468

East Asian (EAS) AF: 0.138 AC: 713 AN: 5180

South Asian (SAS) AF: 0.232 AC: 1116 AN: 4820

European-Finnish (FIN) AF: 0.462 AC: 4881 AN: 10558

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36455 AN: 67994

Other (OTH) AF: 0.427 AC: 900 AN: 2108

Alfa AF: 0.487 Hom.: 91109

Bravo AF: 0.360

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		-0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6465657; hg19: chr7-97816327; COSMIC: COSV51990635;